Social bonding is a naturally rewarding behavior that, like drug reward, is mediated by mesolimbic dopamine (DA). One of the major consequences of drug addiction in humans is disturbed social bonding and reciprocally, strong social attachments have been reported to reduce substance abuse. In the present application, I propose to use the prairie vole model to study the underlying neural mechanisms involved in the interaction of social and drug reward. The prairie vole is a monogamous rodent that forms pair bonds after mating. Mesolimbic DA, particularly in the nucleus accumbens (NAcc), plays an important role in prairie vole social behavior and mediates pair bonding in a DA receptor-specific manner through cAMP signaling. Specifically, D2 receptor (D2R) activation (and the corresponding decrease in cAMP activity) facilitates, and D1 receptor (D1R) activation (and the corresponding increase in cAMP activity) prevents mating-induced pair bonding. We have recently established the prairie vole model as an effective tool for studies of amphetamine (AMPH) reward and its interaction with social behavior. Using the conditioned place preference paradigm, we have found that AMPH is rewarding for the prairie vole, and that DA is involved in AMPH reward. My recent data demonstrate that D1R gene expression is significantly increased inthe NAcc after repeated AMPH injection. Further, our recent data demonstrate that previous AMPH exposure prevents mating-induced pair bonding, indicating that social and drug reward interact in the prairie vole. As NAcc DA receptor specific signaling mediates pair bonding and my recent data demonstrate that AMPH alters NAcc DA in a receptor specific manner, I plan to investigate the involvement of NAcc DA and cAMP activity in the interaction of social behavior and drug reward. I will focus on the molecular consequences of AMPH on NAcc DARs and cAMP signaling and will pharmacologically manipulate these systemsin behavioral experiments to determine their role in social and drug reward interaction. Data from this study could have important implications for both the prevention and treatment of drug addiction.